Direct crosstalk between mast cell-TNF and TNFR1-expressing endothelia mediates local tissue inflammation

被引：49

作者：

Kneilling, Manfred ^{[1
]}

Mailhammer, Reinhard ^{[2
]}

Hueltner, Lothar ^{[2
]}

Schoenberger, Tanja ^{[3
]}

Fuchs, Kerstin ^{[1
]}

Schaller, Martin ^{[1
]}

Bukala, Daniel ^{[4
]}

Massberg, Steffen ^{[5
,6
]}

Sander, Christian A. ^{[7
]}

Braumueller, Heidi ^{[1
]}

Eichner, Martin ^{[8
]}

Maier, Konrad L. ^{[9
]}

Hallmann, Rupert ^{[10
]}

Pichler, Bernd J. ^{[4
]}

Haubner, Roland ^{[11
]}

Gawaz, Meinrad ^{[3
]}

Pfeffer, Klaus ^{[12
]}

Biedermann, Tilo ^{[1
]}

Roecken, Martin ^{[1
]}

机构：

[1] Univ Tubingen, Dept Dermatol, D-72076 Tubingen, Germany

[2] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Clin Mol Biol & Tumor Genet, Munich, Germany

[3] Univ Tubingen, Dept Med 3, Tubingen, Germany

[4] Univ Tubingen, Dept Radiol, Werner Siemens Fdn, Lab Preclin Imaging & Imaging Technol, Tubingen, Germany

[5] Tech Univ Munich, Dept Med, Munich, Germany

[6] Tech Univ Munich, Deutsch Herzzentrum, Munich, Germany

[7] St Georg Hosp, Dept Dermatol, Hamburg, Germany

[8] Univ Tubingen, Dept Med Biometry, Tubingen, Germany

[9] German Res Ctr Environm Hlth, Inst Inhalat Biol, Helmholtz Zentrum Munchen, Munich, Germany

[10] Univ Munster, Inst Physiol Chem & Pathobiochem, D-4400 Munster, Germany

[11] Univ Innsbruck, Dept Nucl Med, A-6020 Innsbruck, Austria

[12] Univ Dusseldorf, Dept Microbiol, Dusseldorf, Germany

来源：

BLOOD | 2009年 / 114卷 / 08期

基金：

美国国家卫生研究院;

关键词：

TUMOR-NECROSIS-FACTOR; CONTACT HYPERSENSITIVITY RESPONSE; INTERCELLULAR-ADHESION MOLECULE-1; VERSUS-HOST-DISEASE; FACTOR-RECEPTOR; T-CELLS; P-SELECTIN; MICE DEFICIENT; ULTRAVIOLET-B; FACTOR-ALPHA;

D O I：

10.1182/blood-2008-11-187682

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Signaling through tumor necrosis factor receptor 1 (TNFR1) controls bacterial infections and the induction of inflammatory Th1 cell-mediated autoimmune diseases. By dissecting Th1 cell-mediated delayed-type hypersensitivity responses (DTHRs) into single steps, we localized a central defect to the missing TNFR1 expression by endothelial cells (ECs). Adoptive transfer and mast cell knockin experiments into Kit(W)/Kit(W-v), TNF-/-, and TNFR1(-/-) mice showed that the signaling defect exclusively affects mast cell-EC interactions but not T cells or antigen-presenting cells. As a consequence, TNFR1(-/-) mice had strongly reduced mRNA and protein expression of P-selectin, E-selectin, ICAM-1, and VCAM-1 during DTHR elicitation. In consequence, intravital fluorescence microscopy revealed up to 80% reduction of leukocyte rolling and firm adhesion in TNFR1(-/-) mice. As substitution of TNF-/- mice with TNF-producing mast cells fully restored DTHR in these mice, signaling of mast cell-derived TNF through TNFR1-expressing ECs is essential for the recruitment of leukocytes into sites of inflammation. (Blood. 2009; 114: 1696-1706)

引用

页码：1696 / 1706

页数：11